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Kazuhiko Nakano - One of the best experts on this subject based on the ideXlab platform.
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Potential involvement of Streptococcus mutans possessing Collagen Binding Protein Cnm in infective endocarditis.
Scientific reports, 2020Co-Authors: Ryota Nomura, Shuhei Naka, Masatoshi Otsugu, Masakazu Hamada, Saaya Matayoshi, Noboru Teramoto, Naoki Iwashita, Michiyo Matsumoto-nakano, Kazuhiko NakanoAbstract:Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing Collagen-Binding Protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV Collagen, and fibrinogen (p
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potential involvement of streptococcus mutans possessing Collagen Binding Protein cnm in infective endocarditis
Scientific Reports, 2020Co-Authors: Ryota Nomura, Shuhei Naka, Masatoshi Otsugu, Masakazu Hamada, Saaya Matayoshi, Noboru Teramoto, Naoki Iwashita, Michiyo Matsumotonakano, Kazuhiko NakanoAbstract:Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing Collagen-Binding Protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV Collagen, and fibrinogen (p < 0.001). Microarray analyses of HUVECs infected by Cnm-positive or -negative S. mutans strains identified several transcripts that were differentially upregulated during invasion, including those encoding the small G Protein regulatory Proteins ARHGEF38 and ARHGAP9. Upregulation of these Proteins occurred during invasion only in the presence of serum. Knockdown of ARHGEF38 strongly reduced HUVEC invasion by Cnm-positive S. mutans. In a rat model of infective endocarditis, cardiac endothelial cell damage was more prominent following infection with a Cnm-positive strain compared with a Cnm-negative strain. These results suggest that the type IV Collagen-Cnm-ARHGEF38 pathway may play a crucial role in the pathogenesis of infective endocarditis.
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Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions
Clinical and Experimental Nephrology, 2020Co-Authors: Shuhei Naka, Ryota Nomura, Michiyo Matsumoto-nakano, Taro Misaki, Kaoruko Wato, Yasuyuki Nagasawa, Kazuhiko NakanoAbstract:Background IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses Collagen-Binding Protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. Methods Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague–Dawley rats to evaluate their kidney conditions. Results The urinary Protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days ( P
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Abstract WMP108: Brain-Oral Axis: Cnm-Positive S. mutans Infection is a Novel Risk Factor for Cerebral Bleeding
Stroke, 2019Co-Authors: Satoshi Hosoki, Ryota Nomura, Kazuhiko Nakano, Shuichi Tonomura, Kazunori Toyoda, Satoshi Saito, Hiroyuki Ishiyama, Masafumi IharaAbstract:Introduction: We previously reported that oral Streptococcus mutans expressing a Collagen Binding Protein Cnm was associated with deep cerebral microbleeds (CMBs) and intracranial hemorrhage (ICH)....
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A Potential New Risk Factor for Stroke: Streptococcus Mutans With Collagen-Binding Protein.
World neurosurgery, 2018Co-Authors: Chikanori Inenaga, Ryota Nomura, Takashi Ooshima, Kazuhiko Nakano, Shuhei Naka, Kazuya Hokamura, Toshihiko Ohashi, Nagato Kuriyama, Toshimitsu Hamasaki, Koichiro WadaAbstract:Background Among human oral bacteria, particular kinds of Streptococcus mutans (SM) known as dental caries pathogens contain a Collagen-Binding Protein, Cnm, and show platelet aggregation inhibition and matrix metalloProteinase-9 activation. We have previously reported that these strains may be a risk factor for intracerebral hemorrhage. As a major sample-providing hospital, we report the clinical details, including intracranial aneurysms and ischemic stroke. Methods After the study received approval from the Ethical Committee, 429 samples of whole saliva were obtained from patients who were admitted to or visited our hospital between February 16, 2010, and February 28, 2011. The study cohort comprised 48 patients with cardioembolic stroke (CES), 151 with non-CES infarct, 54 with intracerebral hemorrhage (ICH), 43 with ruptured intracranial aneurysm (RIA), and 97 with unruptured intracranial aneurysm (UIA). Cultured SM was identified as Cnm-positive when the corresponding gene was positive. The results were compared with those from 79 healthy volunteers. Relationships between Cnm-positive SM and known risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, were analyzed. Results A statistically significant high Cnm-positive rate was observed in patients with CES, non-CES infarct, ICH, and RIA (P = 0.002, 0.039, 0.013, and 0.009, respectively). There were no relationships between Cnm-positive SM and known risk factors. Conclusions Specific types of oral SM can be a risk factor for cardioembolic infarct, intracerebral hemorrhage, and intracranial aneurysm rupture. Further study is needed.
Ryota Nomura - One of the best experts on this subject based on the ideXlab platform.
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Potential involvement of Streptococcus mutans possessing Collagen Binding Protein Cnm in infective endocarditis.
Scientific reports, 2020Co-Authors: Ryota Nomura, Shuhei Naka, Masatoshi Otsugu, Masakazu Hamada, Saaya Matayoshi, Noboru Teramoto, Naoki Iwashita, Michiyo Matsumoto-nakano, Kazuhiko NakanoAbstract:Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing Collagen-Binding Protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV Collagen, and fibrinogen (p
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potential involvement of streptococcus mutans possessing Collagen Binding Protein cnm in infective endocarditis
Scientific Reports, 2020Co-Authors: Ryota Nomura, Shuhei Naka, Masatoshi Otsugu, Masakazu Hamada, Saaya Matayoshi, Noboru Teramoto, Naoki Iwashita, Michiyo Matsumotonakano, Kazuhiko NakanoAbstract:Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing Collagen-Binding Protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV Collagen, and fibrinogen (p < 0.001). Microarray analyses of HUVECs infected by Cnm-positive or -negative S. mutans strains identified several transcripts that were differentially upregulated during invasion, including those encoding the small G Protein regulatory Proteins ARHGEF38 and ARHGAP9. Upregulation of these Proteins occurred during invasion only in the presence of serum. Knockdown of ARHGEF38 strongly reduced HUVEC invasion by Cnm-positive S. mutans. In a rat model of infective endocarditis, cardiac endothelial cell damage was more prominent following infection with a Cnm-positive strain compared with a Cnm-negative strain. These results suggest that the type IV Collagen-Cnm-ARHGEF38 pathway may play a crucial role in the pathogenesis of infective endocarditis.
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Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions
Clinical and Experimental Nephrology, 2020Co-Authors: Shuhei Naka, Ryota Nomura, Michiyo Matsumoto-nakano, Taro Misaki, Kaoruko Wato, Yasuyuki Nagasawa, Kazuhiko NakanoAbstract:Background IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses Collagen-Binding Protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. Methods Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague–Dawley rats to evaluate their kidney conditions. Results The urinary Protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days ( P
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Abstract WMP108: Brain-Oral Axis: Cnm-Positive S. mutans Infection is a Novel Risk Factor for Cerebral Bleeding
Stroke, 2019Co-Authors: Satoshi Hosoki, Ryota Nomura, Kazuhiko Nakano, Shuichi Tonomura, Kazunori Toyoda, Satoshi Saito, Hiroyuki Ishiyama, Masafumi IharaAbstract:Introduction: We previously reported that oral Streptococcus mutans expressing a Collagen Binding Protein Cnm was associated with deep cerebral microbleeds (CMBs) and intracranial hemorrhage (ICH)....
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A Potential New Risk Factor for Stroke: Streptococcus Mutans With Collagen-Binding Protein.
World neurosurgery, 2018Co-Authors: Chikanori Inenaga, Ryota Nomura, Takashi Ooshima, Kazuhiko Nakano, Shuhei Naka, Kazuya Hokamura, Toshihiko Ohashi, Nagato Kuriyama, Toshimitsu Hamasaki, Koichiro WadaAbstract:Background Among human oral bacteria, particular kinds of Streptococcus mutans (SM) known as dental caries pathogens contain a Collagen-Binding Protein, Cnm, and show platelet aggregation inhibition and matrix metalloProteinase-9 activation. We have previously reported that these strains may be a risk factor for intracerebral hemorrhage. As a major sample-providing hospital, we report the clinical details, including intracranial aneurysms and ischemic stroke. Methods After the study received approval from the Ethical Committee, 429 samples of whole saliva were obtained from patients who were admitted to or visited our hospital between February 16, 2010, and February 28, 2011. The study cohort comprised 48 patients with cardioembolic stroke (CES), 151 with non-CES infarct, 54 with intracerebral hemorrhage (ICH), 43 with ruptured intracranial aneurysm (RIA), and 97 with unruptured intracranial aneurysm (UIA). Cultured SM was identified as Cnm-positive when the corresponding gene was positive. The results were compared with those from 79 healthy volunteers. Relationships between Cnm-positive SM and known risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, were analyzed. Results A statistically significant high Cnm-positive rate was observed in patients with CES, non-CES infarct, ICH, and RIA (P = 0.002, 0.039, 0.013, and 0.009, respectively). There were no relationships between Cnm-positive SM and known risk factors. Conclusions Specific types of oral SM can be a risk factor for cardioembolic infarct, intracerebral hemorrhage, and intracranial aneurysm rupture. Further study is needed.
Shuhei Naka - One of the best experts on this subject based on the ideXlab platform.
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Potential involvement of Streptococcus mutans possessing Collagen Binding Protein Cnm in infective endocarditis.
Scientific reports, 2020Co-Authors: Ryota Nomura, Shuhei Naka, Masatoshi Otsugu, Masakazu Hamada, Saaya Matayoshi, Noboru Teramoto, Naoki Iwashita, Michiyo Matsumoto-nakano, Kazuhiko NakanoAbstract:Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing Collagen-Binding Protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV Collagen, and fibrinogen (p
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potential involvement of streptococcus mutans possessing Collagen Binding Protein cnm in infective endocarditis
Scientific Reports, 2020Co-Authors: Ryota Nomura, Shuhei Naka, Masatoshi Otsugu, Masakazu Hamada, Saaya Matayoshi, Noboru Teramoto, Naoki Iwashita, Michiyo Matsumotonakano, Kazuhiko NakanoAbstract:Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing Collagen-Binding Protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV Collagen, and fibrinogen (p < 0.001). Microarray analyses of HUVECs infected by Cnm-positive or -negative S. mutans strains identified several transcripts that were differentially upregulated during invasion, including those encoding the small G Protein regulatory Proteins ARHGEF38 and ARHGAP9. Upregulation of these Proteins occurred during invasion only in the presence of serum. Knockdown of ARHGEF38 strongly reduced HUVEC invasion by Cnm-positive S. mutans. In a rat model of infective endocarditis, cardiac endothelial cell damage was more prominent following infection with a Cnm-positive strain compared with a Cnm-negative strain. These results suggest that the type IV Collagen-Cnm-ARHGEF38 pathway may play a crucial role in the pathogenesis of infective endocarditis.
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Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions
Clinical and Experimental Nephrology, 2020Co-Authors: Shuhei Naka, Ryota Nomura, Michiyo Matsumoto-nakano, Taro Misaki, Kaoruko Wato, Yasuyuki Nagasawa, Kazuhiko NakanoAbstract:Background IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses Collagen-Binding Protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. Methods Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague–Dawley rats to evaluate their kidney conditions. Results The urinary Protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days ( P
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A Potential New Risk Factor for Stroke: Streptococcus Mutans With Collagen-Binding Protein.
World neurosurgery, 2018Co-Authors: Chikanori Inenaga, Ryota Nomura, Takashi Ooshima, Kazuhiko Nakano, Shuhei Naka, Kazuya Hokamura, Toshihiko Ohashi, Nagato Kuriyama, Toshimitsu Hamasaki, Koichiro WadaAbstract:Background Among human oral bacteria, particular kinds of Streptococcus mutans (SM) known as dental caries pathogens contain a Collagen-Binding Protein, Cnm, and show platelet aggregation inhibition and matrix metalloProteinase-9 activation. We have previously reported that these strains may be a risk factor for intracerebral hemorrhage. As a major sample-providing hospital, we report the clinical details, including intracranial aneurysms and ischemic stroke. Methods After the study received approval from the Ethical Committee, 429 samples of whole saliva were obtained from patients who were admitted to or visited our hospital between February 16, 2010, and February 28, 2011. The study cohort comprised 48 patients with cardioembolic stroke (CES), 151 with non-CES infarct, 54 with intracerebral hemorrhage (ICH), 43 with ruptured intracranial aneurysm (RIA), and 97 with unruptured intracranial aneurysm (UIA). Cultured SM was identified as Cnm-positive when the corresponding gene was positive. The results were compared with those from 79 healthy volunteers. Relationships between Cnm-positive SM and known risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, were analyzed. Results A statistically significant high Cnm-positive rate was observed in patients with CES, non-CES infarct, ICH, and RIA (P = 0.002, 0.039, 0.013, and 0.009, respectively). There were no relationships between Cnm-positive SM and known risk factors. Conclusions Specific types of oral SM can be a risk factor for cardioembolic infarct, intracerebral hemorrhage, and intracranial aneurysm rupture. Further study is needed.
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Distribution of Streptococcus mutans strains with Collagen-Binding Proteins in the oral cavity of IgA nephropathy patients.
Clinical and experimental nephrology, 2014Co-Authors: Taro Misaki, Ryota Nomura, Shuhei Naka, Keiko Kuroda, Tempei Shiooka, Yoshitaka Naito, Yumiko Suzuki, Hideo Yasuda, Taisuke Isozaki, Kazuhiko NakanoAbstract:Background IgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis; however, its precise initiating pathogenesis remains unclear. Streptococcus mutans is a major pathogen of human dental caries. S. mutans strains with the cnm gene encoding Cnm, a Collagen-Binding Protein, have been reported to contribute to the development of systemic diseases. However, the contribution of S. mutans with Cnm in the development of IgAN has not been reported. The aim of this study was to investigate the prevalence of cnm-positive S. mutans in IgAN patients and clarify the effects of cnm-positive S. mutans on the histological pathology of IgAN.
B. D. Sanwal - One of the best experts on this subject based on the ideXlab platform.
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Parallel regulation of proCollagen I and colligin, a Collagen-Binding Protein and a member of the serine protease inhibitor family.
The Journal of cell biology, 1993Co-Authors: Elke P. Clarke, N. Jain, Anne Brickenden, Ian A. J. Lorimer, B. D. SanwalAbstract:A potential regulatory linkage between the biosynthesis of colligin, a Collagen-Binding Protein of the ER, and proCollagen I was examined under a variety of experimental conditions. Cell lines which did not produce a significant amount of proCollagen I mRNA also lacked the capacity to produce colligin mRNA. Anchorage-dependent cell lines like L6 myoblasts and normal rat kidney fibroblasts produced both colligin and proCollagen I mRNA, but the level of both was concurrently reduced considerably in their ras-transformed counterparts. Similarly, during the differentiation of L6 myoblasts, levels of both colligin and proCollagen declined together. Treatment of myoblasts by dexamethasone or EGF led to a decrease in the steady-state levels of proCollagen I mRNA, and this was, again, accompanied by a decrease in colligin mRNA synthesis. On the other hand, when the rate of proCollagen I synthesis was stimulated by treatment of myoblasts with TGF beta, it led to the concurrent augmentation of both the mRNA and Protein levels of colligin. A linkage between the regulation of synthesis of proCollagen I and colligin thus seems to exist. The only exception to this generalization is provided by the heat induction behavior of the two Proteins. Treatment of myoblasts for a very short period leads to an increase in the synthesis of both the mRNA and Protein levels of colligin. This, however, is not accompanied by a change in the mRNA levels of proCollagen I. These studies establish that colligin and proCollagen are generally tightly co-regulated except after heat shock, suggesting an important functional linkage.
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Cloning of a human Collagen-Binding Protein, and its homology with rat gp46, chick hsp47 and mouse J6 Proteins.
Biochimica et biophysica acta, 1992Co-Authors: Elke P. Clarke, B. D. SanwalAbstract:Several cDNA clones encoding a Collagen-Binding Protein were isolated from human fibroblasts. The cDNA encoded a 417 amino acid Protein, containing two potential N-linked oligosaccharide Binding sites and a C-terminal RDEL sequence, which has been shown to act as an endoplasmic retention signal in other systems. The derived amino acid sequence of the Protein shows close homology with gp46 from rat skeletal myoblasts, J6 Protein from mouse F9 embryonal carcinoma cells and hsp47 from chick embryo fibroblasts. It also shows sequence similarity with members of the serpin family.
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A Collagen-Binding Protein in the endoplasmic reticulum of myoblasts exhibits relationship with serine protease inhibitors.
The Journal of biological chemistry, 1991Co-Authors: Elke P. Clarke, George A. Cates, Eric H. Ball, B. D. SanwalAbstract:Abstract Several cDNA clones encoding a 46-kDa Collagen-Binding glycoProtein (gp46) from rat skeletal myoblasts were isolated and sequenced. The cDNA encoded a 17-amino acid signal peptide and a 400-amino acid mature Protein, containing three potential N-linked oligosaccharide attachment sites. The cDNA sequence of gp46 shows 93% identity in the coding region with J6, a retinoic acid-inducible gene coding for a Protein of unknown function described from embryonal carcinoma F9 cells. The first 41 NH2-terminal amino acids of the predicted J6 sequence are, however, different from the gp46 sequence as a result of a 7-base pair insertion in the gp46 cDNA. In addition, the NH2-terminal amino acid sequence of hsp47, a Collagen-Binding Protein found in chick embryo fibroblasts, shows 64% identity to gp46 over 36 residues. Interestingly, this alignment begins 10 residues inward from the first amino acid in the mature form of gp46. A significant sequence similarity was observed between gp46 and members of the serine protease inhibitor (serpin) family. Unlike other serpins, however, gp46 is both a heat shock and a Collagen-Binding Protein and is localized to the lumen of the endoplasmic reticulum, as suggested by the presence of the RDEL sequence at the COOH terminus. This sequence is similar to other proposed endoplasmic reticulum retention signals.
Hans C Van Leeuwen - One of the best experts on this subject based on the ideXlab platform.
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clostridium difficile secreted pro pro endopeptidase ppep 1 zmp1 cd2830 modulates adhesion through cleavage of the Collagen Binding Protein cd2831
FEBS Letters, 2015Co-Authors: Paul J. Hensbergen, Dennis Bakker, Michelle L Kelly, Oleg I Klychnikov, Ed J. Kuijper, Irina Dragan, Nigel P Minton, Jan W Drijfhout, Jeroen Corver, Hans C Van LeeuwenAbstract:The Clostridium difficile cd2830 gene product is a secreted metalloprotease, named Pro-Pro endopeptidase (PPEP-1). PPEP-1 cleaves C. difficile cell surface Proteins (e.g. CD2831). Here, we confirmed that PPEP-1 has a unique preference for prolines surrounding the scissile bond. Moreover, we show that it exhibits a high preference for an asparagine at the P2 position and hydrophobic residues at the P3 position. Using a PPEP-1 knockout C. difficile strain, we demonstrate that the removal of the Collagen Binding Protein CD2831 is fully attributable to PPEP-1 activity. The PPEP-1 knockout strain demonstrated higher affinity for Collagen type I with attenuated virulence in hamsters.
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Clostridium difficile secreted Pro-Pro endopeptidase PPEP-1 (ZMP1/CD2830) modulates adhesion through cleavage of the Collagen Binding Protein CD2831.
FEBS Letters, 2015Co-Authors: Paul J. Hensbergen, Dennis Bakker, Michelle L Kelly, Oleg I Klychnikov, Ed J. Kuijper, Irina Dragan, Nigel P Minton, Jan W Drijfhout, Jeroen Corver, Hans C Van LeeuwenAbstract:The Clostridium difficile cd2830 gene product is a secreted metalloprotease, named Pro-Pro endopeptidase (PPEP-1). PPEP-1 cleaves C. difficile cell surface Proteins (e.g. CD2831). Here, we confirmed that PPEP-1 has a unique preference for prolines surrounding the scissile bond. Moreover, we show that it exhibits a high preference for an asparagine at the P2 position and hydrophobic residues at the P3 position. Using a PPEP-1 knockout C. difficile strain, we demonstrate that the removal of the Collagen Binding Protein CD2831 is fully attributable to PPEP-1 activity. The PPEP-1 knockout strain demonstrated higher affinity for Collagen type I with attenuated virulence in hamsters.